Long-Term Olanzapine Treatment: Weight Change and Weight-Related Health Factors in Schizophrenia

Background: Weight change and the weight-relatedhealth factors of nonfasting serum glucose, serum cholesterol,and diastolic blood pressure levels were analyzed in patientswith DSM-III-R schizophrenia and related disorders who receivedtreatment with olanzapine for up to 3 years, and comparisons weremade to patients treated with haloperidol. Baseline body massindex (BBMI; kg/m²) and dose (mg/day) wereinvestigated as predictors of long-term weight change experiencedduring olanzapine treatment.

Method: This analysis retrospectively examined573 patients receiving olanzapine and 103 patients receivinghaloperidol for 39 weeks or more from a study of 1996 patientsrandomly assigned 2:1 to either olanzapine, 5 to 20 mg/day, orhaloperidol, 5 to 20 mg/day. After 6 weeks of acute therapy,patients continued for 1 year or more with either double-blind oropen-label olanzapine therapy or double-blind haloperidoltherapy.

Results: Mean weight gain for olanzapine-treatedpatients observed for a median of 2.54 years trended toward aplateau after the first 39 weeks of treatment with alast-observation-carried-forward mean weight change of 6.26 kg(13.8 lb) and a median of 5.90 kg (13.0 lb). This wassignificantly higher than that for haloperidol-treated patients,whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p 27.6) gainedsignificantly less weight during treatment with olanzapine thantheir lighter counterparts (BBMI < 27.6) (p =.183). Median serum glucose at endpoint was not significantlyassociated (p = .096) with weight change for olanzapine. Medianserum cholesterol and diastolic blood pressure forolanzapine-treated patients at endpoint showed a relationshipwith weight change that was statistically (p .05).

Conclusion: Mean weight gain duringolanzapine treatment trended toward a plateau after theinitial 39 weeks of treatment with no further significant gainout to 3 years. Higher BBMI was predictive of a lower long-termweight gain, while dose was not a significant predictor ofgreater longer term weight change. The relationship betweenweight change and glucose was not statistically significant. Theassociation between weight change and changes in cholesterol aswell as changes in diastolic blood pressure was statisticallysignificant but not considered clinically relevant based on theranges observed.